This proposal is for continuation of four year renewal of research in the natural history, epidemiology, statistical conduct, design, collation and treatment of childhood malignant diseases in a sophisticated multimodal manner. This institution has been a member of the Children's Cancer Study Group since 1959. Over the past 20 years a very strong referral pattern for children with malignant disease has been established throughout the Pacific Northwest and continues to grow. From October 1, 1978 through July 31, 1979, 92 children were seen with childhood malignancies and treated on Children's Cancer Group protocols. Thirty-one of these were leukemia and 61 were solid tumors. In addition, 12 more patients with acute leukemia were treated on a pilot protocol with the National Cancer Institute, Pediatric Division, in conjunction with Dr. A. Bleyer of this institution and Dr. Poplack of the NCI Pediatric Division. This study will be piloted primarily in the use of high-dose intravenous methotrexate in an effort to successfully treat CNS leukemia. In addition to the Children's Cancer Study Group programs we are continuing collaboration with Dr. E. Donnall Thomas in bone marrow transplantation. Eighteen bone marrow transplants have been done in this hospital since October 1, 1978. Also continuing is Dr. I. Bernstein's work in tumor immunology, particularly with emphasis on monoclonal antibody studies done in mice and we hope to soon transfer this to human leukemia cells. Dr. W.A. Bleyer continues to work with the National Cancer Institute in his high-dose methotrexate pharmacologic studies and intraventricular methotrexate studies and also aminopterin. This program continues as pediatric oncology unit at the Fred Hutchinson Cancer Research Center.